alpha1-adrenergic-receptor responsiveness in skeletal muscle during dynamic exercise

Attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during dynamic exercise is controversial. One potential mechanism is a reduction in alpha1-adrenergic-receptor responsiveness. The purpose of this study was to examine alpha1-adrenergic-receptor-mediated vasoconstriction in resting and working skeletal muscles by using intra-arterial infusions of a selective agonist. Seven mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. A selective alpha1-adrenergic-receptor agonist (phenylephrine) was infused as a bolus into the femoral artery catheter at rest and during exercise. All dogs ran on a motorized treadmill at two exercise intensities (3 and 6 miles/h). Intra-arterial infusions of the same effective concentration of phenylephrine elicited reductions in vascular conductance of 76 +/- 4, 76 +/- 6, and 67 +/- 5% (P > 0.05) at rest, 3 miles/h, and 6 miles/h, respectively. Systemic blood pressure and blood flow in the contralateral iliac artery were unaffected by phenylephrine. These results do not demonstrate an attenuation of vasoconstriction to a selective alpha1-agonist during exercise and do not support the concept of sympatholysis.     

Somatostatin-stimulated growth hormone-releasing factor secretion in vitro is modified by fetal ethanol exposure

1. The mechanism of neurogenic regulation of skeletal muscle circulation was studied in the hindlimb of anaesthetized rats in vivo. Regional blood flow (RBF) of the hindlimb was recorded with a pulsed Doppler flow probe positioned in the iliac artery. 2. A short period (1 min) of sciatic nerve stimulation at 10 Hz caused a sustained increase in RBF (from 2.0 +/- 0.2 to 3.7 +/- 0.2 kHz at the peak), but no appreciable change in either MBP or HR, suggesting that the nerve stimulation produced local vasodilatation of the peripheral vasculature. The hyperaemic response reached a peak within 15 s and characteristically remained above the basal level for more than 5 min after the cessation of nerve stimulation. The response was regarded as a secondary response brought about by the contraction of skeletal muscles since (+)-tubocurarine (0.73 micromol kg(-1), i.a.) almost abolished it. 3. Lignocaine (43 micromol kg(-1), i.a.) and capsaicin (0.33 micromol kg(-1), i.a.) significantly suppressed the hyperaemic response to skeletal muscle contraction, suggesting that capsaicin-sensitive sensory nerves contribute to the hyperaemia. In contrast, an inhibitor of NO synthase, N(omega)-nitro-L-arginine methyl ester (1 micromol kg(-1) min(-1), i.v.), did not affect the hyperaemic response. 4. Serum levels of calcitonin gene-related peptide (CGRP) in iliac venous effluent significantly increased from 51 +/- 4 to 77 +/- 5 fmol ml(-1) during the hyperaemic response to skeletal muscle contraction. A bolus injection of CGRP (300 pmol kg(-1), i.a.) induced a long-lasting increase in RBF of the hindlimb. Moreover, CGRP(8-37) (100 nmol kg(-1) min(-1), i.v.), a specific CGRP1 receptor antagonist, significantly suppressed the hyperaemic response, especially the sustained phase of the response which was almost abolished by this antagonist. 5. These results suggest that CGRP, which is released from peripheral endings of capsaicin-sensitive sensory nerves, partly mediates the hyperaemia evoked by skeletal muscle contraction of the rat hindlimb.     

Renal and intrarenal blood flow distribution in swine during severe exercise

It is known that a compensatory reduction and diversion of renal flow occurs in severe exercise in humans but not in dogs. We investigated this in miniature swine by measuring changes in total renal blood flow (TRF) and intra-renal blood flow (IRBF) distribution with tracer microspheres (15 +/- 5 mum) at rest and during steady-state exercise at 4.8-7.2 kph and 0% grade, and during severe exercise at 4.8-7.2 kph and 10% grade. We measured heart rate and cardiac output (Q) via implanted probes. TRF was determined as a percent of Q and as ml/100 g per min. IRBF was determined for the outer cortex, inner cortex, outer medulla, and inner medulla. Our results show that renal blood flow is significantly (P less than 0.05) reduced in pigs with exercise. Steady-state exercise reduced flow to about 66% of control and severe exercise reduced renal flow to 30% of control. IRBF was unchanged throughout. These results show that the exercising pig augments blood flow to skeletal muscle by reducing blood flow to kidneys, a response known to occur in man.     

Treatment of a maxillary defect following resection of carcinoma

BACKGROUND: Adenosine has been proposed to be a locally produced regulator of blood flow in skeletal muscle. However, the fundamental questions of to what extent adenosine is formed in skeletal muscle tissue of humans, whether it is present in the interstitium, and where it exerts its vasodilatory effect remain unanswered. METHODS AND RESULTS: The interstitial adenosine concentration was determined in the vastus lateralis muscle of healthy humans via dialysis probes inserted in the muscle. The probes were perfused with buffer, and the dialysate samples were collected at rest and during graded knee extensor exercise. At rest, the interstitial concentration of adenosine was 220+/-100 nmol/L and femoral arterial blood flow (FaBF) was 0.19+/-0.02 L/min. When the subjects exercised lightly, at a work rate of 10 W, there was a markedly higher (1140+/-540 nmol/L; P<0.05) interstitial adenosine concentration and a higher FaBF (2.22+/-0.18 L/min; P<0.05) compared with at rest. When exercise was performed at 20, 30, 40, or 50 W, the concentration of adenosine was moderately greater for each increment, as was the level of leg blood flow. The interstitial concentrations of ATP, ADP, and AMP increased from rest (0.13+/-0.03, 0.07+/-0.03, and 0.07+/-0.02 micromol/L, respectively) to exercise (10 W; 2.00+/-1.32, 2.08+/-1.23, and 1.65+/-0.50 micromol/L, respectively; P<0.05). CONCLUSIONS: The present study provides, for the first time, interstitial adenosine concentrations in human skeletal muscle and demonstrates that adenosine and its precursors increase in the exercising muscle interstitium, at a rate associated with intensity of muscle contraction and the magnitude of muscle blood flow.     

Genetic aspects of Crohn disease and ulcerative colitis. Empirical risk of recurrence and case presentation

Nutrient uptake by the hindlimb was investigated utilising the arteriovenous difference technique in 5 Thoroughbred horses fed to maintenance a diet of 100% roughage or 52% oat grain and 48% roughage. Arterial blood was obtained from a catheter inserted into the carotid artery while venous blood was simultaneously collected from a catheter placed into the iliac vein via the medial saphenous vein. The arteriovenous difference for glucose was significant and represented a mean extraction of 10 +/- 1% with no effect of diet. If fully oxidised, glucose uptake (corrected for lactate and pyruvate arteriovenous difference) was sufficient to account for 78 +/- 13% or 107 +/- 15% of the oxygen consumed by the hindlimb in horses fed a roughage or 52% oat grain diet respectively. Acetate was also a major metabolite of the hindlimb, showing a 39 +/- 5% extraction with no effect of diet. However, the 52% oat grain diet did induce a significant decline in the concentration of acetate in arterial blood. The potential contribution to oxidation in the hindlimb was significantly reduced from 32 +/- 4% in horses fed roughage to 21 +/- 3% when fed 52% oat grain. D-3-Hydroxybutyrate uptake could account for 9 +/- 1% of the oxidation by the hindlimb with no effect of diet. The technique for measuring nutrient uptake across the hindlimb using the arteriovenous difference is relatively simple and would be valuable in investigating fuel use by muscle during exercise.     

Maintained exercise pressor response in heart failure

The impact of forearm blood flow limitation on muscle reflex (metaboreflex) activation during exercise was examined in 10 heart failure (HF) (NYHA class III and IV) and 9 control (Ctl) subjects. Rhythmic handgrip contractions (25% maximal voluntary contraction, 30 contractions/min) were performed over 5 min under conditions of ambient pressure or with +50 mmHg positive pressure about the exercising forearm. Mean arterial blood pressure (MAP) and venous effluent hemoglobin (Hb) O2 saturation, lactate and H+ concentrations ([La] and [H+], respectively) were measured at baseline and during exercise. For ambient contractions, the increase (Delta) in MAP by end exercise (DeltaMAP; i.e., the exercise pressor response) was the same in both groups (10.1 +/- 1.2 vs. 7.33 +/- 1.3 mmHg, HF vs. Ctl, respectively) despite larger Delta[La] and Delta[H+] for the HF group (P < 0.05). With ischemic exercise, the DeltaMAP for HF (21.7 +/- 2.7 mmHg) exceeded that of Ctl subjects (12.2 +/- 2.8 mmHg) (P < 0.0001). Also, for HF, Delta[La] (2.94 +/- 0.4 mmol) and Delta[H+] (24.8 +/- 2.7 nmol) in the ischemic trial were greater than in Ctl (1.63 +/- 0.4 mmol and 15.3 +/- 2.8 nmol; [La] and [H+], respectively) (P < 0.02). Hb O2 saturation was reduced in Ctl from approximately 43% in the ambient trial to approximately 27% with ischemia (P < 0.0001). O2 extraction was maximized under ambient exercise conditions for HF but not for Ctl. Despite progressive increases in blood perfusion pressure over the course of ischemic exercise, no improvement in Hb O2 saturation or muscle metabolism was observed in either group. These data suggest that muscle reflex activation of the pressor response is intact in HF subjects but the resulting improvement in perfusion pressure does not appear to enhance muscle oxidative metabolism or muscle blood flow, possibly because of associated increases in sympathetic vasoconstriction of active skeletal muscle.     

Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea

The effects of methoctramine, a cardioselective muscarinic cholinergic antagonist, on heart rate and small intestinal motor activity were compared to those of the nonselective competitive muscarinic antagonist, atropine. Methoctramine or atropine, 6, 10, 30, 60 micrograms/kg, or sterile isotonic saline, was administered intravenously to six conscious dogs in cross-over studies. Methoctramine administration caused dose-dependent tachycardia without affecting intestinal motility, while atropine administration caused dose-dependent tachycardia accompanied by significant reductions in small intestinal motility. Additionally, methoctramine did not inhibit intestinal smooth muscle contractile activity initiated by the muscarinic agonist bethanechol, while atropine inhibited bethanechol-induced contractile activity in a dose-dependent manner. Calculated, dosages of methoctramine and atropine required to produce a 50% increase in heart rate over baseline were 35.1 +/- 5.3 and 39.5 +/- 6.2 micrograms/kg, respectively. This dosage of atropine caused a 93 +/- 13.9% reduction in intestinal motility. These findings suggest that selective muscarinic antagonists may be useful drugs for those veterinary patients in which nonselective muscarinic antagonists have the potential to produce untoward effects on intestinal motility.     

A two-dimensional Kolmorogov-Smirnov test for binned data

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.     

Augmented mesenteric and renal vasoconstriction during exercise in senescent Fischer 344 rats

The purpose of this study was to test the hypothesis that vasoconstriction in the mesenteric and renal circulations is greater at both submaximal and maximal exercise intensities with advancing age. Arterial blood pressure, heart rate, and mesenteric, renal, and iliac (hindlimb) artery blood flow velocities were measured before and during graded treadmill exercise in mature (12 mo) and senescent (24 mo) male Fischer 344 rats. During treadmill running at mild, moderate, and maximal exercise intensities (approximately 45, 70, and 100% of maximal oxygen uptake), the increases in arterial pressure were similar in the mature and senescent animals, whereas heart rate rose less in the older group (P < 0.05). Mesenteric and renal flow velocities declined and vascular resistances increased from resting levels in both groups in response to graded exercise; however, the magnitudes of the increases in both mesenteric and renal vascular resistance were significantly augmented in the older rats at the moderate and maximal workloads. Hindlimb blood flow velocity increased and resistance declined from resting levels at each exercise intensity in both groups. In contrast to the visceral and renal adjustments, the magnitudes of the changes in both hindlimb flow and resistance were similar for the two age groups at all exercise intensities. These findings support the hypothesis that mesenteric and renal vasoconstriction is augmented in senescent Fischer 344 rats during exercise at moderate and maximal intensities but not at mild workloads. Despite these regional differences, the maintenance of arterial pressure is not altered at either submaximal or maximal exercise intensities with advancing age.     

Variation in phosphoric acid concentration and treatment time and HEMA diffusion through dentin

IGF-1 and its receptors have been identified in many tissues including the central nervous system (CNS). We have previously demonstrated that injection of insulin directly into the cerebral ventricles (ICV) is followed by a drop in mean arterial pressure (MAP) associated with an increase in skeletal muscle blood flow. Given the similarities between the IGF-1 and insulin molecules and their respective receptors, we have investigated the effect of ICV administration of IGF-1 on systemic blood pressure and blood flow in selected vascular beds. ICV cannulas were implanted into normal rats and the animals were allowed to recover for 3 to 4 days. The femoral artery and vein were cannulated for blood pressure monitoring and blood sampling and blood flow probes placed around the iliac, the renal and the superior mesenteric artery were used to assess regional blood flow. ICV injection of IGF-1 resulted in a significant decrease in MAP with a nadir at 15 minutes and a gradual return to baseline by 60 minutes; heart rate increased 40 minutes after the injection. IGF-1 significantly enhanced vascular flow and conductance in the iliac, but not in the renal and superior mesenteric arteries. The effects of IGF-1 were much smaller than those observed previously with equimolar amounts of insulin. We conclude that IGF-1 can decrease MAP by selectively increasing blood flow to skeletal muscle through a direct action on the central nervous system.     

Impact of alpha-adrenergic coronary vasoconstriction on the transmural myocardial blood flow distribution during humoral and neuronal adrenergic activation

Increased heart rate and left ventricular pressure during humoral and neuronal adrenergic activation act to restrict blood flow preferentially in the subendocardium. The hypothesis was advanced that alpha-adrenergic coronary vasoconstriction preferentially in the subepicardium may counterbalance the enhanced extravascular compression in the subendocardium and serve to maintain blood flow transmurally uniform. In 40 anesthetized dogs, regional myocardial blood flow was determined with colored microspheres; wall function, with sonomicrometry. Humoral adrenergic activation (HAA) was induced by a combination of intravenous atropine, intravenous norepinephrine, and atrial pacing during baseline coronary vasomotor tone (group 1, n = 6) and in the presence of maximal coronary vasodilation with intravenous dipyridamole (group 2, n = 6). In an additional group, HAA was induced by intravenous norepinephrine in the presence of dipyridamole but without atropine and atrial pacing in order to increase end-diastolic left ventricular pressure (group 3, n = 6). Measurements were performed at rest, during HAA, and during ongoing HAA with the intracoronary infusion of the alpha-antagonist phentolamine (Phen). At unchanged mean aortic pressure, Phen improved blood flow particularly to the inner layers as follows: from 1.42 +/- 0.40 (mean +/- SD) to 1.90 +/- 0.40 mL/(min.g) (group 1, P < .05), from 4.99 +/- 2.31 to 5.53 +/- 2.56 mL/(min.g) (group 2, P < .05), and from 6.01 +/- 1.41 to 6.29 +/- 1.27 mL/(min.g) (group 3, P < .05), associated with a decrease in outer layer blood flow in groups 2 and 3. In 16 additional dogs, beta-adrenoceptors were blocked by propranolol and muscarinic receptors by atropine. Neuronal adrenergic activation (NAA) was induced by cardiac sympathetic nerve stimulation (CSNS) during baseline coronary vasomotor tone (group 4, n = 8) and in the presence of maximal vasodilation (group 5, n = 8). Measurements were performed at rest, during a first CSNS, and 20 minutes later during a second CSNS+Phen. The reproducibility of two consecutive episodes of CSNS 20 minutes apart was demonstrated in a separate set of experiments (n = 6). At matched mean aortic pressures, Phen improved blood flow to all myocardial layers in group 4, whereas in group 5, Phen induced a redistribution of myocardial blood flow toward subepicardial layers [from 4.44 +/- 0.96 to 4.81 +/- 0.83 mL/(min.g), P < .05] at the expense of inner layers. With the addition of Phen, there was no change in regional wall function in any group of dogs studied. Thus, during HAA, alpha-adrenergic coronary vasoconstriction does not exert a beneficial effect on transmural blood flow distribution. During NAA, a beneficial effect of alpha-adrenergic coronary vasoconstriction becomes apparent only under conditions of maximal coronary vasodilation.     

Role of the vascular endothelium in O2 extraction during progressive ischemia in canine skeletal muscle

O2 extraction during progressive ischemia in canine skeletal muscle, J. Appl. Physiol. 79(4): 1351-1360, 1995.--O2 uptake (VO2) is defended during decreased O2 delivery (QO2) by an increase in the O2 extraction ratio (O2ER, VO2/QO2), presumably by recruitment of capillaries. This study tested the hypothesis that activity of the microvascular endothelium plays a necessary role in achievement of maximal O2ER. We pump perfused the vascularly isolated hindlimbs of 24 anesthetized and paralyzed dogs at progressively lower flows over a 90-min period. In eight dogs, hindlimb vascular endothelium was removed by injection of deoxycholate (DOC) into the perfusing artery before the ischemic challenge. DOC treatment resulted in loss of normal in vivo and in vitro endothelium-dependent dilatory responses to acetylcholine, but endothelium-independent vascular smooth muscle responses were intact. Eight other dogs were pretreated with nitro-L-arginine methyl ester plus indomethacin (L+I group) to block the synthesis of the vasodilators nitric oxide and prostacyclin. L+I and DOC treatment were associated with increases in hindlimb vascular resistance of 168 +/- 17 and 63 +/- 12%, respectively. O2ER at critical QO2 (QO2 at which VO2 begins to decrease) was 81 +/- 2% in eight control dogs, 66 +/- 6% in L+I, and 42 +/- 4% in DOC, indicating a significant O2 extraction defect in the two treatment groups. These data suggest that products of the vascular endothelium play an important role in the matching of O2 supply to demand during supply limitation in skeletal muscle.     

Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.     

Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3 microg/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidaprilat or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrite) concentrations of coronary venous blood were markedly increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either imidaprilat or cilazaprilat in the low constant coronary blood flow condition. It is concluded that ACE inhibitors can increase cardiac NO levels via the accumulation of bradykinin in the ischemic myocardium.     

Rat hindlimb muscle blood flow during level and downhill locomotion

During eccentrically biased exercise (e.g., downhill locomotion), whole body oxygen consumption and blood lactate concentrations are lower than during level locomotion. These general systemic measurements indicate that muscle metabolism is lower during downhill exercise. This study was designed to test the hypothesis that hindlimb muscle blood flow is correspondingly lower during downhill vs. level exercise. Muscle blood flow (determined by using radioactive microspheres) was measured in rats after 15 min of treadmill exercise at 15 m/min on the level (L, 0 degrees) or downhill (D, -17 degrees). Blood flow to ankle extensor muscles was either lower (e.g., white gastrocnemius muscle: D, 9 +/- 2; L, 15 +/- 1 ml. min-1. 100 g-1) or not different (e.g., soleus muscle: D, 250 +/- 35; L, 230 +/- 21 ml. min-1. 100 g-1) in downhill vs. level exercise. In contrast, blood flow to ankle flexor muscles was higher (e.g., extensor digitorum longus muscle: D, 53 +/- 5; L, 31 +/- 6 ml. min-1. 100 g-1) during downhill vs. level exercise. When individual extensor and flexor muscle flows were summed, total flow to the leg was lower during downhill exercise (D, 3.24 +/- 0.08; L, 3.47 +/- 0. 05 ml/min). These data indicate that muscle blood flow and metabolism are lower during eccentrically biased exercise but are not uniformly reduced in all active muscles; i.e., flows are equivalent in several ankle extensor muscles and higher in ankle flexor muscles.     

Characterization of dose-dependent metabolic responses to close arterial infusion of cimaterol in the hindlimb of steers

Dose-dependent effects of cimaterol (CIM) on hindlimb metabolism were determined in six steers (247 +/- 22 kg BW) using a close arterial infusion. The external iliac vessels of both hindlimbs were catheterized to accommodate measurement of blood flow, circulating concentrations, and net flux of NEFA, lactate, and alpha-amino nitrogen (AAN) during infusion of CIM at 0, .05, .1, .3, .7, 1 and 3 micrograms/ min. Close arterial infusion of CIM in the hindlimb of steers can be used to achieve a local concentration elevation that is required to differentiate local and systemic effects in vivo. Calculated plasma threshold CIM concentration required to initiate cardiovascular responses was 21 pg/mL, which resulted from an infusion rate of .3 microgram/min. Threshold concentrations of CIM for stimulation of NEFA and lactate net flux in the hindlimb were 38 and 34 pg/mL, respectively, and would be achieved with an infusion rate of .7 microgram/min. All measured responses except AAN net flux exhibited significant linear and quadratic dose effects, and responses in the treated hindlimb were always severalfold greater than in the contralateral control hindlimb. Maximal differences between treated and control hindlimb blood flow occurred with a CIM infusion rate of .7 microgram/min, but the highest infusion rate (3 micrograms/min) was required to maximize differences in NEFA and lactate flux. Therefore, to minimize cardiovascular and other systemic responses and optimize direct hindlimb responses, an infusion rate of .5 microgram of CIM/ min should cause significant stimulation of beta-adrenergic receptors only in the CIM-infused hindlimb of young, growing steers.     

Autoradiographic studies on the uptake of 3H-noradrenaline and 3H-GABA in cultured rat cerebellum

Vasoconstriction due to parallel i.a. injections of NA were studied in subcutaneous adipose tissue and gracilis muscle preparations in dogs. The vasoconstrictor response to NA was significantly lower in adipose tissue than in muscle. Only in muscle did acidosis inhibit NA-induced vasoconstriction. The beta-receptor antagonist propranolol increased the vasoconstrictor response in adipose tissue to the level of skeletal muscle. The lack of significant inhibition of NA-induced vasoconstriction in adipose tissue may be due to the simultaneous inhibition of two opposing mechanisms-alpha-adrenergic vasoconstriction and beta-adrenergic vasodilatation. After propranolol acidosis inhibited NA-induced vasoconstriction equally in adipose tissue and muscle. The difference between adipose tissue and muscle may thus be due to a greater importance of a beta-adrenergic vasodilator mechanism in the former tissue. The metabolic response to isoprenaline was inhibited by acidosis, while the direct vasodilatation was unaffected. It is suggested that the beta-adrenergic vasodilator mechanism that is inhibited by acidosis is related to the metabolism of the tissue.     

Effect of consecutive administration of obsidan and novodrin on pulmonary circulation in anesthesized dogs

It was established in experiments on mongrel anesthesized dogs that the beta-blocking agent obsidan (propranolol) in a dose of 0.5-1.0 mg/kg causes an increase in total pulmonary and pulmono-arteriole resistance, which correlates with the decrease in volume blood flow in the pulmonary arteries. The pressure in the pulmonary artery and the left atrium does not change substantially. Injection of 0.25-0.5 mg of novodrin increases the volume blood flow, causes no effect on pressure in the left atrium, and reduces total pulmonary resistance. The changes occurring in pulmonary circulation under the effect of beta-adrenergic agents depend on their primary action on cardiac activity whereas the increase in total pulmonary and pulmono-arteriole resistance depends on the secondary spasm of the pulmonary vessels.     

Serum-derived immunosuppressive substances. I. Partial purification and range of action

The role of sympathetic mechanisms in mediating the pulmonary vasoconstrictor response to respiratory acidosis was studied in intact dogs. Arterial oxygen tension and ventilation were maintained at resting levels and the response was studied during a constant level of alpha- and beta-adrenergic blockade. There were significant increases in the pulmonary vascular resistance (PVR) and pulmonary perfusion pressure and no change in pulmonary blood flow (Q) when the dogs breathed 5% CO2 for 10 min. The alpha-adrenergic blocking agent, phenoxybenzamine, did not significantly alter the pulmonary vascular response, while the beta-adrenergic blocking agent, propranolol, enhanced the response. Phenoxybenzamine significantly reduced the resting pulmonary perfusion pressure from control values, while propranolol did not alter it. Both propranolol and phenoxybenzamine produced comparable decreases in the resting Q from control values. The resting PVR increased to a greater extent with propranolol than with phenoxybenzamine. These results indicate that adrenergic mechanisms do not play a role in mediating rise in PVR induced by respiratory acidosis. The finding that the pulmonary vasoconstrictor response to respiratory acidosis is enhanced during beta-adrenergic blockade suggests that vasoconstrictor alpha-receptors may be unmasked during beta-adrenergic blockade. Finally, the studies suggest that both alpha- and beta-receptors contribute to maintaining the resting PVR.